Abstract
Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35-55-immunized FABP(-/-) mice showed reduced proliferation and impaired IFN-gamma production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP(-/-) dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology
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Brain / metabolism
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Brain / pathology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Disease Progression
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / prevention & control*
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Fatty Acid-Binding Proteins / biosynthesis
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Fatty Acid-Binding Proteins / deficiency*
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Fatty Acid-Binding Proteins / genetics
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Glycoproteins / administration & dosage
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Glycoproteins / immunology
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Spinal Cord / metabolism
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Spinal Cord / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
Substances
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Fatty Acid-Binding Proteins
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Glycoproteins
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Inflammation Mediators
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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myelin oligodendrocyte glycoprotein (35-55)